P-TOLUENE SULFONYL ISOCYANATE

P-Toluene Sulfonyl Isocyanate is a highly reactive organic isocyanate with the formula C₈H₇NO₃S, derived from p-toluenesulfonic acid and isocyanic acid.
P-Toluene Sulfonyl Isocyanate is widely used in organic synthesis as an electrophilic reagent for introducing sulfonyl and isocyanate functionalities, particularly in the preparation of sulfonamides, ureas, carbamates, and heterocyclic compounds.
P-Toluene Sulfonyl Isocyanate must be handled under dry, controlled conditions and is considered toxic and moisture-sensitive.

CAS Number: 4083-64-1
Molecular Formula: C8H7NO3S
Molecular Weight: 197.21
EINECS Number: 223-810-8

Synonyms: Tosyl isocyanate, p-Toluenesulfonyl isocyanate, 4083-64-1, 4-Methylbenzenesulfonyl isocyanate, p-Toluenesulphonyl isocyanate, Benzenesulfonyl isocyanate, 4-methyl-, Additive TI, H9004FJX6V, DTXSID1027558, DTXCID407558, RefChem:1094233, 223-810-8, 4-methyl-N-(oxomethylidene)benzenesulfonamide, PtSi, p-Tolylsulfonyl isocyanate, 4-methylbenzene-1-sulfonyl isocyanate, p-toluenesulfonylisocyanate, p-Toluenesulfonic acid, anhydride with isocyanic acid, p-Tosyl isocyanate, MFCD00002030, p-Methylphenylsulfonyl isocyanate, 4-Methylphenylsulfonyl isocyanate, p-TOLUENE SULFONYL ISOCYANATE, 4-Toluenesulfonyl isocyanate, (4-methylphenyl)sulfonylisocyanate, EINECS 223-810-8, CAS-4083-64-1, UNII-H9004FJX6V, TosNCO, TsNCO, 4-Methylbenzene-1-sulphonyl isocyanate, 4-methyl-N-(oxomethylene)benzenesulfonamide, p-tolylsulfonyl-isocyanate, Sulfone, isocyanato tolyl, p-toluenesulphonylisocyanate, p-Toluensulfonyl isocyanate, EC 223-810-8, p-toluene sulfonylisocyanate, p-Toluenesulfonyl lsocyanate, p-toluene-sulfonyl isocyanate, para-toluenesulfonylisocyanate, SCHEMBL22302, 4-Isocyanatosulphonyltoluene, p-toluene sulphonyl isocyanate, para-toluene sulfonylisocyanate, 4-toluene-sulphonyl isocyanate, CHEMBL1879981, VLJQDHDVZJXNQL-UHFFFAOYSA-, 4-Methylphenylsulphonyl isocyanate, 4-methyl-benzenesulfonyl isocyanate, p-Toluenesulfonyl isocyanate, 96%, Tox21_201698, Tox21_303136, BBL011351, SBB063168, STL146441, AKOS000119298, NCGC00164078-01, NCGC00164078-02, NCGC00257105-01, NCGC00259247-01, P-METHYLBENZENESULFONYL ISOCYANATE, PS-10276, DB-049668, NS00009877, ST50825414, T0998, 4-methyl-N-(oxo-methylene)-benzenesulfonamide, EN300-19005, E76074, F494399, Q27279783, F0001-1154, ISOCYANIC ACID, ANHYDRIDE WITH P-TOLUENESULFONIC ACID, p-Toluenesulfonyl isocyanate, for HPLC derivatization, ≥98.0% (HPLC), InChI=1/C8H7NO3S/c1-7-2-4-8(5-3-7)13(11,12)9-6-10/h2-5H,1H3, 4-Isocyanatosulphonyltoluene,;p-Toluenesulfonyl isocyanate, 96%, AcroSeal;Isocyanicacid, anhydride with p-toluenesulfonic acid (6CI);p-Toluenesulfonyl isocyanate 96%;p-Toluenesulfonyl isocyanate, 96%, SpcSeal;p-Toluenesulfonylisocyanate,95%;Benzenesulfonyl isocyanate, 4-methyl-;Benzenesulfonylisocyanate,4-methyl-

P-Toluene Sulfonyl Isocyanate is a moisture scavenger. Urethane systems utilizing PTSI can be applied under the most demanding humidity, dew point or temperature conditions and still guarantee the best corrosion resistance. 
Its reactivity towards active hydrogen atoms makes it useful as a scavenger for water and other isocyanate reactive groups such as free acid in powdered aluminum alkanoates and active hydrogen present in carbon black pigments. 
P-Toluene Sulfonyl Isocyanate is suitable for the formulation of adhesives and sealants. 

P-Toluene Sulfonyl Isocyanate has a minimum shelf life of 1 year.
P-Toluene Sulfonyl Isocyanate is an organic sulfonyl isocyanate compound derived from p-toluenesulfonyl chloride in which the reactive functional group is the isocyanate (–N=C=O).
Its structure combines a p-methylphenyl sulfonyl group with an isocyanate moiety, giving it very high electrophilicity.

Because of this functionality, it is highly reactive toward nucleophiles such as amines, alcohols, and water.
P-Toluene Sulfonyl Isocyanate is typically a colorless to pale yellow liquid that is moisture sensitive.
It readily hydrolyzes in the presence of water, releasing carbon dioxide and forming sulfonamide derivatives.

P-Toluene Sulfonyl Isocyanate must be handled under dry conditions and stored under inert atmosphere when possible.
P-Toluene Sulfonyl Isocyanate acts as a powerful derivatizing and activating reagent.
The sulfonyl group stabilizes reaction intermediates, while the isocyanate group enables rapid formation of ureas and carbamates.

This dual reactivity makes it particularly valuable in selective functional group transformations.
P-Toluene Sulfonyl Isocyanate is widely used in organic synthesis and medicinal chemistry.
It is employed to introduce sulfonylurea or sulfonamide functionalities into molecules.

These structural motifs are important in pharmaceuticals, agrochemicals, and bioactive compound development.
In synthetic methodology, it is used to activate amines and alcohols for further transformation.
P-Toluene Sulfonyl Isocyanate enables mild and efficient formation of protected intermediates or reactive derivatives.

As a result, it is commonly found in multistep laboratory syntheses and fine chemical production.
P-Toluene Sulfonyl Isocyanate is classified as a highly activated sulfonyl isocyanate, and its reactivity is significantly higher than that of simple aromatic isocyanates.
The strong electron-withdrawing sulfonyl group increases polarization of the isocyanate carbon, lowering activation barriers for nucleophilic attack.

This electronic effect explains why reactions often occur rapidly and irreversibly.
In mechanistic terms, reactions with nucleophiles typically proceed through direct addition to the isocyanate carbon followed by rearrangement or stabilization by the sulfonyl group.
Side reactions such as polymerization are minimal under strictly anhydrous conditions.

This predictable mechanism makes it suitable for precise functional-group installation.
P-Toluene Sulfonyl Isocyanate is frequently used to differentiate amines of similar basicity in multifunctional molecules.
Primary amines react faster than secondary ones, enabling selective derivatization.

This selectivity is particularly useful in late-stage modification of complex molecules.
In medicinal and agrochemical chemistry, it is used to introduce metabolically stable sulfonylurea linkages.

These linkages often enhance biological activity and improve pharmacokinetic properties.
As a result, the reagent appears in the synthesis of enzyme inhibitors, herbicides, and lead optimization compounds.

Melting point: 5 °C
Boiling point: 144 °C at 10 mm Hg (lit.)
Density: 1.291 g/mL at 25 °C (lit.)
Vapor pressure: 1 mm Hg at 100 °C
Refractive index: n²⁰/D 1.534 (lit.)
Flash point: >230 °F
Storage temperature: Under inert gas (nitrogen or argon) at 2–8 °C
Form: Liquid
Color: Clear, colorless to yellow
Specific gravity: 1.291
Odor: Acrid odor
Water solubility: Reacts with water
Sensitive: Moisture sensitive
BRN: 391287
InChI: 1S/C₈H₇NO₃S/c1-7-2-4-8(5-3-7)13(11,12)9-6-10/h2-5H,1H₃
InChIKey: VLJQDHDVZJXNQL-UHFFFAOYSA-N
SMILES: Cc1ccc(cc1)S(=O)(=O)N=C=O
LogP: 0.6 at 30 °C

P-Toluene Sulfonyl Isocyanate shows extremely fast reaction kinetics with nucleophilic functional groups because the sulfonyl group strongly withdraws electron density from the isocyanate carbon.
This makes the –N=C=O group more electrophilic than in simple alkyl or aryl isocyanates.
As a result, reactions often proceed at low temperature and without strong catalysts.

In reactions with amines, P-Toluene Sulfonyl Isocyanate forms sulfonyl ureas in high yield.
These products are synthetically valuable because they are stable, crystalline, and easy to purify.
Such sulfonyl urea motifs are common in biologically active molecules and enzyme inhibitors.

When reacted with alcohols or phenols, it forms sulfonyl carbamates.
These intermediates are frequently used as protecting groups or activated species for further substitution reactions.
The reactions are generally clean and selective, which is advantageous in complex molecule synthesis.

P-Toluene Sulfonyl Isocyanate is also used in heterocyclic chemistry.
P-Toluene Sulfonyl Isocyanate can promote cyclization reactions by activating amino or hydroxy groups within the same molecule.
This strategy is useful for constructing nitrogen-containing rings in pharmaceutical intermediates.

From a handling perspective, the compound is highly moisture sensitive and reacts violently with water.
Contact with atmospheric moisture can lead to rapid decomposition and pressure buildup due to carbon dioxide release.
Therefore, it is typically handled in a dry glovebox or under inert gas using anhydrous solvents.

In research laboratories, P-Toluene Sulfonyl Isocyanate is valued for its predictability and high functional-group tolerance under controlled conditions.
Despite its reactivity, it allows precise modification of target molecules without excessive side reactions.
This balance of reactivity and selectivity explains its frequent use in advanced organic synthesis.

P-Toluene Sulfonyl Isocyanate is recommended especially for one‐component, low‐VOC polyurethane coatings. 
The reaction of PTSI with water introduced from pigments and solvents in the paint formulation generates carbon dioxide and soluble inert chemical products. 
Experience has demonstrated that 13 grams of PTSI effectively scavenges 1 gram of water. 

P-Toluene Sulfonyl Isocyanate reacts with water in a 1 to 1 molar ratio, generating PTSA and carbon dioxide gas.
P-Toluene Sulfonyl Isocyanate is stable at room temperature when dry but decomposes upon heating or moisture exposure.
Decomposition pathways include hydrolysis and uncontrolled urea formation.

Therefore, reactions are usually conducted at low to moderate temperatures.
From a practical standpoint, it is supplied and stored under dry, inert conditions due to its high moisture sensitivity.

Even trace water can trigger rapid CO₂ evolution and loss of reactivity.
This sensitivity requires careful handling but also reflects its strong synthetic utility.

Uses Of P-Toluene Sulfonyl Isocyanate:
P-Toluene Sulfonyl Isocyanate is a reagent used to prepare acetylated syn-1,2-diols,oxazolidin-2-ones, 2,3-diamino acids, and N-tosylcarbonamides. -Toluenesulfonyl isocyanate has been used as derivatization reagent in determination of 3-α-hydroxy tibolone in human plasma by LC-MS/MS. 
P-Toluene Sulfonyl Isocyanate is also employed in the derivatization reagent in simultaneous quantitative analysis of diethylene glycol and propylene glycol in pharmaceutical products by HPLC and as reagent in the preparation of acetylated syn-1,2-diols, oxazolidin-2-ones, 2,3-diamino acids and N-tosylcarbonamides.

P-Toluene Sulfonyl Isocyanate is a reagent used to prepare acetylated syn-1,2-diols,1 oxazolidin-2-ones,2 2,3-diamino acids,3 and N-tosylcarbonamides.4
P-Toluene Sulfonyl Isocyanate is primarily used as a highly reactive reagent in organic synthesis.
It is employed to introduce sulfonylurea and sulfonylcarbamate functional groups into organic molecules.

These groups are important structural motifs in pharmaceuticals, agrochemicals, and bioactive compounds.
It is widely used for the derivatization of amines.
Primary and secondary amines react readily to form stable sulfonyl ureas, which are useful intermediates and protecting groups.

This application is especially valuable in multistep synthesis and structure–activity relationship studies.
P-Toluene Sulfonyl Isocyanate is used to activate alcohols and phenols through carbamate formation.
These activated intermediates can undergo further substitution or rearrangement reactions.

This strategy enables selective transformations under mild conditions.
In heterocyclic and medicinal chemistry, it is applied to promote intramolecular cyclization reactions.
By activating nucleophilic sites, it facilitates the construction of nitrogen-containing heterocycles.

Such rings are common in drug candidates and fine chemicals.
P-Toluene Sulfonyl Isocyanate is also used in analytical and mechanistic studies as a derivatizing agent.
Formation of well-defined urea derivatives allows easier characterization and purification of amines.

This improves analytical accuracy in complex reaction systems.
P-Toluene Sulfonyl Isocyanate is used in late-stage functionalization of complex molecules, where high chemoselectivity is required.
It allows selective modification of amino or hydroxy groups without disturbing other sensitive functionalities.

This makes it valuable in medicinal chemistry during lead optimization.
In pharmaceutical intermediate synthesis, it is employed to introduce sulfonylurea linkages that enhance biological activity and stability.
These linkages are common in enzyme inhibitors and receptor-binding molecules.

The reagent enables efficient access to these motifs under relatively mild conditions.
P-Toluene Sulfonyl Isocyanate is applied in agrochemical research for the synthesis of sulfonylurea-based herbicide intermediates.
Such compounds exhibit high potency at low application rates.

p-Toluenesulfonyl isocyanate provides a convenient route to these structures.
In protecting-group chemistry, it is used to temporarily mask amines or alcohols.
The resulting derivatives are stable to many reaction conditions and can be selectively removed later.

This supports complex, multistep synthetic sequences.
P-Toluene Sulfonyl Isocyanate is also used in method development and reaction screening.

P-Toluene Sulfonyl Isocyanates high reactivity makes it a benchmark reagent for studying nucleophilic addition to isocyanates.
These studies help design new reagents and improve synthetic efficiency.

Safety Profile Of P-Toluene Sulfonyl Isocyanate:
Harmful if swallowed, inhaled or absorbed through the skin. 
Causes skin and severe eye irritation. 

P-Toluene Sulfonyl Isocyanate may cause an allergic respiratory response. 
Reacts spontaneously and violently with water, alcohols, amines, acids and alkaline solutions. 
These substances should not be poured into a vessel containing P-Toluene Sulfonyl Isocyanate. 

Prolonged exposure of P-Toluene Sulfonyl Isocyanate to elevated temperatures can result in violent decomposition. 
P-Toluene Sulfonyl Isocyanate is a highly hazardous, reactive chemical due to its isocyanate functionality.
It is toxic by inhalation, ingestion, and skin contact, and even small exposures can cause serious health effects.

The compound readily reacts with moisture, which increases the risk during handling.
Contact with skin or eyes can cause severe irritation, burns, and tissue damage.
P-Toluene Sulfonyl Isocyanate vapors may lead to eye watering, redness, and long-lasting ocular injury.

Protective gloves, goggles, and full skin coverage are essential when handling this substance.
Inhalation poses a significant risk, as isocyanate vapors can irritate the respiratory tract.
Exposure may cause coughing, chest tightness, shortness of breath, and asthma-like symptoms.

Repeated or prolonged exposure can result in respiratory sensitization, making future exposure dangerous even at very low levels.
P-Toluene Sulfonyl Isocyanate reacts violently with water, alcohols, and amines, releasing carbon dioxide gas.

This reaction can cause pressure buildup in closed containers and lead to rupture or explosion.
P-Toluene Sulfonyl Isocyanate must therefore be stored in airtight containers under dry, inert conditions.